Fungicidal compositions

ABSTRACT

N-Acylated N-phenyl-aminotetrahydro-2-furanones of the formula ##STR1## wherein R represents C 1  -C 4  -alkyl, C 1  -C 4  -alkoxy or halogen, 
     R 1  represents C 1  -C 3  -alkyl, C 1  -C 4  -alkoxy or halogen, 
     R 2  represents hydrogen, C 1  -C 3  -alkyl, C 1  -C 4  -alkoxy or halogen, 
     R 3  represents hydrogen or methyl, with the total number of C atoms of the substituents R, R 1 , R 2  and R 3  in the phenyl ring not exceeding the number 8, 
     R 4  represents hydrogen or methyl, while 
     R 5  represents one of the following groups: an alkylthioalkyl or alkoxyalkyl group having 2 to 5 carbon atoms or an alkoxyalkoxymethyl group having a maximum of 6 carbon atoms, a 2-furanyl or 2-tetrahydrofuranyl group optionally substituted by halogen, a 1,2,4-triazolylmethyl group, a 1,2-pyrazolylmethyl group, or a group --CH 2  --OR 6  in which R 6  represents a 5- or 6-membered heterocycle having oxygen as the hetero atom. 
     are valuable fungicidal active substances. They can be used as fungicidal compositions, particularly for combating phytopathogenic fungi, e.g. against downy mildew on potatoes, tomatoes, grape vines and sugar beet and other plants. The novel compounds have a systemic action.

This is a divisional of application Ser. No. 002,490 filed on Jan. 11,1979, now abandoned, which is a divisional of Ser. No. 873,585, filed onJan. 30, 1978, now U.S. Pat. No. 4,147,792.

The present invention relates to compounds of the formula I ##STR2##wherein R represents C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or halogen,

R₁ represents C₁ -C₃ -alkyl, C₁ -C₄ -alkoxy or halogen,

R₂ represents hydrogen, C₁ -C₃ -alkyl, C₁ -C₄ -alkoxy or halogen,

R₃ represents hydrogen or methyl, with the total number of C atoms ofthe substituents R, R₁, R₂ and R₃ in the phenyl ring not exceeding thenumber 8,

R₄ represents hydrogen or methyl, whilst

R₅ represents one of the following groups: an alkylthioalkyl oralkoxyalkyl group having 2 to 5 carbon atoms or an alkoxyalkoxymethylgroup having a maximum of 6 carbon atoms, a 2-furanyl or2-tetrahydrofuranyl group optionally substituted by halogen, a1,2,4-triazolylmethyl group, a 1,2-pyrazolylmethyl group, or a group--CH₂ --OR₆ in which R₆ represents a 5- or 6-membered heterocycle havingoxygen as the hetero atom; to processes for producing these compounds;to compositions containing these compounds as active substances; and tothe use of these active substances as microbicides in the protection ofplants.

By alkyl or as alkyl moiety of an alkylthio or alkoxy group are meant,depending on the given number of carbon atoms, the following groups:methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl ortert.-butyl. Alkoxyalkoxy groups are, in particular, methoxymethoxy,ethoxymethoxy, 1-methoxyethoxy and 1-ethoxyethoxy.

By halogen is meant fluorine, chlorine, bromine or iodine. R₆ representspreferably a tetrahydrofuranyl or pyranyl group, particularly one boundin the 2-position.

In the U.S. Pat. No. 3,933,860 are described3-[N-acyl-N-arylamino]-lactones and -lactams as fungicides which arederived from the structure of benzoyl-, alkanoyl- orhaloalkanoyl-(particularly haloacetyl-)anilides. Anilides of this typeare described in the literature in great numbers as herbicides, e.g.U.S. Pat. Nos. 3,403,994, 3,442,945, 3,547,620, 3,637,847, 3,598,859 or3,946,045.

It is therefore not surprising that the compounds given in U.S. Pat. No.3,933,860 give rise in part, when applied in the amounts required inpractice, to undesirable phytotoxicity in the plants to be protectedfrom fungus infestation.

It has now been found that, surprisingly, compounds having the structureof the formula I have for practical requirements a very favourablemicrobicidal spectrum for the protection of cultivated plants, withoutaffecting them disadvantageously by causing undesirable secondaryeffects. Within the scope of the present invention, cultivated plantsare, for example, grain, maize, rice, vegetables, sugar beet, soyabeans, peanuts, fruit trees and ornamental plants, especially howevergrape vines, hops, cucurbitaceae (cucumbers, pumpkins and melons), andsolanaceae such as potatoes, tobacco and tomatoes, as well as bananas,cocoa plants and natural rubber plants.

Fungi occurring on plants or on parts of plants (fruit, blossom,foliage, stalks, tubers or roots) in these cultivated crops, or inrelated crops, can be inhibited or destroyed by application of theactive substances of the formula I; and also parts of plantssubsequently growing remain protected from such fungi. The activesubstances are effective against the phytopathogenic fungi belonging tothe following classes: Ascomycetes (e.g. Erysiphaceae); Basidiomycetes,such as in particular rust fungi; Fungi imperfecti (e.g. Moniliales);but especially against Oomycetes belonging to the Phycomycetes class,such as Phytophthora, Peronospora, Pseudoperonospora, Pythium orPlasmopara. Furthermore, the compounds of the formula I have a systemicaction. They can be used also as dressing agents for treating seeds(fruits, tubers and grain) and plant cuttings to preserve them fromfungus infections; and they can be used also against phytopathogenicfungi occurring in the soil.

Preferred compounds of the formula I as plant fungicides are thosewherein R represents methyl, R₁ represents methyl, ethyl, chlorine orbromine, R₂ represents hydrogen, halogen or methyl, and R₃ representshydrogen or methyl, while R₄ and R₅ have the meanings given for theformula I. These are to be referred to as compound group Ia.

An important subgroup of the compound group Ia is formed by thosecompounds wherein R₅ represents an alkylthioalkyl or alkoxyalkyl grouphaving 2 to 5 carbon atoms, a 2-furanyl or 2-tetrahydrofuranyl groupoptionally substituted by halogen, or a 1,2,4-triazolylmethyl group.This subgroup is to be called compound group Ib.

Compounds to be emphasised among these compounds of the group Ib byvirtue of their effectiveness are those wherein R₅ representsmethoxymethyl or ethoxymethyl. These are to be called compound group Ic.

Particularly preferred active substances within the compound group Ia,on account of their advantageous action, are those wherein R₅ representsthe 1,2,4-triazol-1-ylmethyl group. These are to be designated ascompound group Id.

A further important subgroup of the compound group Ia is formed by thosecompounds wherein R₅ represents a 2-furanyl or 2-tetrahydrofuranyl groupoptionally substituted by halogen. This subgroup is to be termedcompound group Ie.

Another important subgroup of the compound group Ia is made up of thosecompounds wherein R₅ represents a 1,2-pyrazolymethyl group. Thissubgroup is to be referred to as compound group If.

Yet another important subgroup of the compound group Ia is composed ofthose compounds wherein R₅ represents an alkoxyalkoxymethyl group havinga maximum of 5 carbon atoms. This subgroup is to be identified ascompound group Ig.

The compounds of the formula I are produced according to the invention

(A) by acylation of a compound of the formula II ##STR3## with acompound of the formula III

    Hal'--CO--R.sub.5                                          (III);

or to obtain derivatives with R₅ =1,2,4-triazolylmethyl,1,2-pyrazolylmethyl or alkylthio

(B) by initial monohaloacetylation of a compound of the formula II togive a compound of the formula IV ##STR4## and further reactionselectively with 1,2,4-triazole, 1,2-pyrazole or alkylmerkaptan, or withthe metal salt of one of these reactants, preferably with the alkalimetal salt or alkaline-earth metal salt; or to obtain derivatives withR₅ =alkoxyalkoxymethyl or --CH₂ --OR₆

(C) by initial monohaloacetylation of a compound of the formula II togive a compound of the formula IV, exchange of the reactive substituentHal" for a lower alkanecarboxylic acid, or for one of the alkali metalsalts or alkaline-earth metal salts thereof, to obtain anacyloxyacetylanilide of the formula V ##STR5## from which there is thenobtained by mild alcoholysis with e.g. an alkali alcoholate of a loweralcohol, such as methanol or ethanol, and acidification thecorresponding hydroxyacetanilide, which is activated with alkali metal,alkali hydride or p-toluenesulphonic acid, and reacted selectively withalkoxyalkyl halide or 2,3-dihydrofuran or 3,4-dihydro-2H-pyrane; or

(D) by reaction of an already acylated aniline of the formula VI##STR6## in the presence of a proton acceptor such as butyl-lithium orsodium hydride, with a 2-halo-4-butyrolactone of the formula VII##STR7##

In the formulae II, III, IV, V, VI and VII, the symbols R to R₅ have themeanings given under the formula I, and Halo, Hal' and Hal" representhalogen, preferably chlorine or bromine. R₇ is a lower alkyl grouphaving less than 7 C atoms.

The reactions can be performed in the presence or absence of solvents ordiluents which are inert to the reactants. The following are for examplesuitable: aliphatic or aromatic hydrocarbons such as benzene, toluene,xylenes or petroleum ether; halogenated hydrocarbons such aschlorobenzene, methylene chloride, ethylene chloride or chloroform;ethers and ethereal compounds such as dialkyl ether, dioxane ortetrahydrofuran; nitriles such as acetonitrile; N,N-dialkylated amidessuch as dimethylformamide; dimethylsulphoxide, ketones such as methylethyl ketone, and mixtures of such solvents with each other.

For acylation according to process A or C, or for monohaloacetylationaccording to process B, it is possible to use the correspondingcarboxylic acids themselves and also the esters thereof, advantageouslyhowever the acid anhydrides or, as given in the case of formula III, theacid halides, preferably the acid chlorides or acid bromides.

The reaction temperatures are between 0° and 180° C., preferably between20° and 120°. The use of acid-binding agents or condensation agents isadvantageous in some cases. Suitable as such are tertiary amines such astrialkylamines (e.g. triethylamine), pyridine and pyridine bases, orinorganic bases, such as the oxides and hydroxides, hydrogen carbonatesand carbonates of alkali metals and alkaline-earth metals, and alsosodium acetate.

The production process A starting with compounds of the formula II, andlikewise the acylation stage leading to compounds of the formula IV, canbe performed also without acid-binding agents; in some cases, however,the passing through of nitrogen to expel the formed hydrogen halide inadvisable. In other cases, an addition of dimethylformamide as areaction catalyst is very advantageous.

Details regarding the production of the intermediates of the formula IIare known.

The compounds of the formula I possess in the lactone radical ##STR8## a(*) center of asymmetry and, where R₄ =CH₃, a second (**) center ofasymmetry, and can be resolved in the customary manner (e.g. fractionalcrystallisation or chromatographical separation) into optical antipodes.In this respect, the different configurations have a varyingly strongmicrobicidal action. Centers of asymmetry can occur also in the case ofsome substituents R₅. Provided that no specific synthesis for theisolation of the pure isomers of the formula I or of the employedbutyrolactone is performed, a product is usually obtained as an isomericmixture.

The following Examples serve to further illustrate the invention withouthowever limiting the scope thereof. The temperatures are in degreesCentigrade.

The following compounds belong to a class of particularly effectiveplant fungicides:

3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-aminotetrahydro-2-furanone,

3-[N-(ethoxyacetyl)-N-(2,6-dimethylphenyl)]-aminotetrahydro-2-furanone,

3-[N-(methoxyacetyl)-N-(2,6-dimethyl-3-chlorophenyl)]-aminotetrahydro-2-furanone,

3-[N-(ethoxyacetyl)-N-(2,6-dimethyl-3-chlorophenyl)]-aminotetrahydro-2-furanone,

3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino-5-methyltetrahydro-2-furanone,

2,6-dimethyl-N-(3-tetrahydrofuran-2-one)-2-tetrahydrofuroyl-anilide,

2,3,6-trimethyl-N-(3-tetrahydrofuran-2-one)-2-tetrahydrofuroyl-anilide,

2,6-dimethyl-4-chloro-N-(3-tetrahydrofuran-2-one)-2-tetrahydrofuroyl-anilide,

3-[N-(methoxyacetyl)-N-(2,3,5,6-tetramethylphenyl)]-aminotetrahydro-2-furanone,and

2,3,5,6-tetramethyl-N-(3-tetrahydrofuran-2-one)-2-furoylanilide.

EXAMPLE 1

Production of ##STR9##

3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino-tetrahydro-2-furanone(compound No. 2)

(a) 165 g of 2-bromo-4-butyrolactone is slowly added to 121 g of2,6-dimethylaniline and 106 g of sodium carbonate in 750 ml ofdimethylformamide, and then stirred for 30 hours at 100°. After cooling,the unreacted aniline and the solvent are distilled off in vacuo; theresidue is added to water and extracted three times with methylenechloride. The extracts are washed with water, dried over sodiumsulphate, and then freed from solvent. After recrystallisation frompetroleum ether/diethyl ether (1:10), the residue melts at 79°-83°.

(b) 11.9 g of methoxyacetyl chloride in 20 ml of toluene is added, withstirring, to 20.5 g of the intermediate product, obtained according to(a), in 80 ml of abs. toluene, whereupon the temperature rises from 25°to 35°. The reaction mixture is refluxed for six hours and, after theaddition of active charcoal, filtered through Hyflo; it is thenconcentrated by evaporation and recrystallised from ethylacetate/petroleum ether, m.p. 124°-127°.

EXAMPLE 2

Production of ##STR10##

N-(3'-tetrahydrofuranone-2')-N-ethoxymethoxyacetyl-2,3,6-trimethylaniline(compound No. 14)

(a) 0.5 g of sodium is dissolved in 10 ml of absolute methanol. There isthen added dropwise, with stirring, a solution of 21.4 g of3-[N-acetoxyacetyl)-N-(2,3,6-trimethylphenyl)]-aminotetrahydro-2-furanonein 60 ml of abs. methanol at 20°-25°. Stirring is continued overnight atroom temperature; the reaction mixture is subsequently concentrated in arotary evaporator, and 500 ml of ice water is added. The suspension isthen adjusted with 1% hydrochloric acid, with ice cooling, to pH 2(acidified to Congo red); it is filtered with suction and then washedwith water until neutral. The3-[N-(hydroxyacetyl)-N-(2,3,6-trimethylphenyl)]-aminotetrahydrofuranone-2,occurring as a mixture of diastereoisomers, has a melting point of151°-155° after being recrystallised from isopropanol.

(b) In a nitrogen atmosphere, 1.3 g of sodium hydride (as a 55% oildispersion) is suspended in 50 ml of abs. tetrahydrofuran. There is thenadded dropwise at 0°-10° 13.8 g of the intermediate product obtainedunder (a), dissolved in 50 ml of abs. tetrahydrofuran. After completionof the generation of hydrogen (3 hours), a solution of 4.7 g ofchloromethylethyl ether in 10 ml of tetrahydrofuran is added dropwise at0°, and stirring is maintained for 20 hours at room temperature. Wateris then carefully added, and extraction with ether is performed fourtimes. The extracts are washed with water and dried over sodiumsulphate. Concentration by evaporation yields a resin which, for theremoval of paraffin oil, is digested four times with a small amount ofpetroleum ether; the elementary analysis of the resin obtained gives thefollowing values:

found: C, 64.1%, H, 7.7% N, 4.0%, calculated: C, 64.4% H, 7.5% N, 4.2%.

EXAMPLE 3

Production of ##STR11##

N-(3"-tetrahydrofuranone-2")-N-2'-pyranyloxyacetyl-2,6-dimethylaniline(compound No. 43)

13.2 g of the3-[N-hydroxyacetyl-N-(2,6-dimethyl-phenyl)]-amino-tetrahydrofuranone-2obtained in a manner analogous to that described in Example 2a issuspended in 50 ml of abs. ethyl acetate, and a trace ofp-toluenesulphonic acid is added. There is then added dropwise at roomtemperature in the course of 10 minutes, with stirring, a solution of5.9 g of 3,4-dihydro-2-H-pyrane in 10 ml of abs. ethyl acetate. Thereaction mixture is then stirred for a further 11/4 hours at roomtemperature; it is subsequently cooled to 0° and 15 g of solid potassiumcarbonate is added. After stirring at 0° for 15 minutes, the mixture isfiltered; thorough washing is then carried out with ethyl acetate, andthe filtrate is concentrated by evaporation. On trituration withpetroleum ether, the residue crystallises, and melts at 106°-112°(diastereoisomeric mixture).

There are produced in an analogous manner the following compounds of theformula

    __________________________________________________________________________     ##STR12##                                                                    (R = CH.sub.3)                                                                (R.sub.1 = 6-position)                                                        Compound                           Physical                                   No.   R.sub.1                                                                          R.sub.2                                                                           R.sub.3                                                                           R.sub.4                                                                          R.sub.5        constants                                  __________________________________________________________________________    1     CH.sub.3                                                                         H   H   CH.sub.3                                                                         CH.sub.2 OCH.sub.3                                                                           m.p. 109-110°                       2     CH.sub.3                                                                         H   H   H  CH.sub.2 OCH.sub.3                                                                           m.p. 124-127°                       5     C.sub.2 H.sub.5                                                                  H   H   H  CH.sub.2 OCH.sub.3                                        4     CH.sub.3                                                                         H   H   CH.sub.3                                                                         CH.sub.2 OC.sub.2 H.sub.5                                 5     CH.sub.3                                                                         H   H   H  CH.sub.2 OC.sub.2 H.sub.5                                                                    oil                                        6     Cl H   H   H  CH.sub.2 OCH.sub.3                                        7     CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 OCH(CH.sub.3)OC.sub.2 H.sub.5                                                       resin                                      8     CH.sub.3                                                                         H   H   H  CH.sub.2 OC.sub.3 H.sub.7 (n)                             9     CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 OCH.sub.3                                                                           resin                                      10    Cl H   H   H  CH.sub.2 OC.sub.2 H.sub.5                                 11    Br 4-Cl                                                                              H   H  CH.sub.2 OCH.sub.3                                        12    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 OC.sub.2 H.sub.5                                                                    resin                                      13    CH.sub.3                                                                         4-Cl                                                                              H   H  CH.sub.2 CH.sub.2 OCH.sub.3                               14    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 OCH.sub.2 OC.sub.2 H.sub.5                                                          resin                                      15    CH.sub.3                                                                         3-CH.sub.3                                                                        H   CH.sub.3                                                                         CH.sub.2 OCH.sub.3                                        16    CH.sub.3                                                                         H   H   H  CH.sub.2 OC.sub.3 H.sub.7 (i)                             17    CH.sub.3                                                                         H   H   H  CH.sub.2 CH.sub.2 OCH.sub.3                                                                  b.p. 178-185°/                                                         0.1 Torr                                   18    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H  CH.sub.2 OC.sub.3 H.sub.7 (i)                             19    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H  CH.sub.2 OCH.sub.3                                                                           m.p. 111-114°                       20    CH.sub.3                                                                         4-Cl                                                                              H   H  CH.sub.2 OC.sub.2 H.sub.5                                                                    m.p. 105-106°                       21    CH.sub.3                                                                         3-CH.sub.3                                                                        H   CH.sub.3                                                                         CH.sub.2 CH.sub.2 OCH.sub.3                               22    CH.sub.3                                                                         H   H   H  CH.sub.2 OCH.sub.2 OCH.sub.3                                                                 oil                                        23    CH.sub.3                                                                         3-CH.sub.3                                                                        H   CH.sub.3                                                                         CH.sub.2 OC.sub.2 H.sub.5                                 24    CH.sub.3                                                                         4-Cl                                                                              H   H  CH.sub.2 OCH.sub.3                                                                           m.p. 111-113°                       25    CH.sub.3                                                                         H   H   H  CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                                                           b.p. 160-165°/                                                         0.2 Torr                                   26    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H  CH.sub.2 OC.sub.2 H.sub.5                                                                    m.p. 81-83°                         27    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2SCH.sub.3                                                                            m.p. 90-94°                         28    CH.sub.3                                                                         H   H   H  CH.sub.2SCH.sub.3                                                                            m.p. 72-73°                         29    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H                                                                                 ##STR13##     m.p. 88-91°                         30    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 OCH.sub.3                                                                           b.p. 190-200°/                                                         0.1 Torr                                   31    CH.sub.3                                                                         4-Cl                                                                              H   CH.sub.3                                                                         CH.sub.2 OCH.sub.3                                        32    CH.sub.3                                                                         H   H   H  CH.sub.2 CH.sub.2 OC.sub.3 H.sub.7 (i)                    33    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 OC.sub.2 H.sub.5                                                                    b.p. 120-135°/                                                         0.08 Torr                                  34    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H  CH.sub.2 CH.sub.2 OCH.sub.3                               35    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 OC.sub.3 H.sub.7 (n)                             36    CH.sub.3                                                                         4-Cl                                                                              H   CH.sub.3                                                                         CH.sub.2 OC.sub.2 H.sub.5                                 37    CH.sub.3                                                                         H   H   H  CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3                                                        b.p. 186-195°/                                                         0.1 Torr                                   38    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 OC.sub.3 H.sub.7 (i)                             39    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 OCH.sub.2 CH.sub.2 OCH.sub.3                                                        oil                                        40    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                                                           b.p. 190-193°/                                                         0.15 Torr                                  41    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 CH.sub.2 OCH.sub.3                               42    CH.sub.3                                                                         3-Cl                                                                              H   H  CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5                        43    CH.sub.3                                                                         H   H   H                                                                                 ##STR14##     b.p. 106-112°                       44    CH.sub.3                                                                         H   H   H  CH.sub.2 OCH(CH.sub.3)OC.sub.2 H.sub.5                                                       oil                                        45    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H  CH.sub.2 OCH(CH.sub.3)OC.sub.2 H.sub.5                                                       oil                                        46    CH.sub.3                                                                         3-CH.sub.3                                                                        H   H  CH.sub.2 CH.sub.2 OCH.sub.3                                                                  b.p. 182-185°/                                                         0.08 Torr                                  47    CH.sub.3                                                                         3-CH.sub.3                                                                        5-CH.sub.3                                                                        H                                                                                 ##STR15##     m.p. 93-97°                         __________________________________________________________________________

and also the following derivatives with R=--OCH₃ and R₄ =H:

    ______________________________________                                        Compound                              Physical                                No.      R.sub.1                                                                              R.sub.2                                                                              R.sub.3                                                                            R.sub.5   constants                               ______________________________________                                        48       CH.sub.3                                                                             H      H    --CH.sub.2 OCH.sub.3                                                                    m.p. 88-90°                      49       Cl     H      H    --CH.sub.2 OCH.sub.3                                                                    m.p. 79-83°                      50       Br     4-Cl   H    --CH.sub.2 OCH.sub.3                              ______________________________________                                    

EXAMPLE 4

Production of ##STR16##

3-[N-(1,2,4-triazol-1-yl-acetyl)-N-(2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanone(compound No. 61)

(a) 165 g of 2-bromo-4-butyrolactone is slowly added at 10° to 135 g of2,3,6-trimethylaniline and 106 g of sodium carbonate in 750 ml ofdimethylformamide, and the mixture is subsequently stirred for 16 hoursat 70° and for 24 hours at 100°. After cooling to +10°, there is added,with cooling, 1200 ml of ice water. Stirring is maintained at 10° for 2hours; the precipitate is filtered off and subsequently washed withwater and petroleum ether to leave3-[N-(2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanone, m.p.108°-110°.

(b) 11 g of the intermediate product obtained according to (a) isrefluxed in 60 ml of abs. toluene with 6.2 g of chloroacetyl chloridefor 4 hours; the solvent is distilled off after cooling, and thebrownish-coloured residue is recrystallised from ethyl acetate/petroleumether (b.p. 40°-60°) to yield3-[N-chloroacetyl-N-(2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanone,m.p. 92°-94°.

(c) 5.6 g of 1,2,4-triazole is added portionwise, in a nitrogenatmosphere, to 2.4 g of 50% sodium hydride dispersion in 100 ml of abs.dioxane, and refluxing is maintained until the generation of hydrogenhas ceased. After cooling to +10°, there is added dropwise, withstirring, 8 g of the3-[N-chloroacetyl-N-(2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanonein 100 ml of dioxane; the reaction mixture is refluxed for 16 hours in anitrogen atmosphere and, after cooling, 100 ml of water is carefullyadded. The mixture is poured into ice water, and repeatedly extractedwith methylene chloride. The combined extracts are washed with water,dried over sodium sulphate, filtered, and freed from solvent. Afterdissolving the residue in ethyl acetate, the solution is boiled withactive charcoal and filtered hot, and petroleum ether (b.p. 40°-60°) isadded to the still hot filtrate until it starts to become cloudly; thefiltrate is then cooled and the final product is filtered off. On beingheated, it commences to slowly decompose from 70°.

There are produced in an analogous manner the following compounds of theformula

    ______________________________________                                         ##STR17##                                                                    (R.sub.1 = 6-position)                                                        Compound                                Physical                              No.     R       R.sub.1                                                                              R.sub.2                                                                             R.sub.3                                                                             R.sub.4                                                                            data                                  ______________________________________                                        51      CH.sub.3                                                                              CH.sub.3                                                                             H     H     H    m.p. 133-135°                  52      CH.sub.3                                                                              Cl     H     H     CH.sub.3                                   53      CH.sub.3                                                                              C.sub.2 H.sub.5                                                                      H     H     H                                          54      CH.sub.3                                                                              Cl     H     H     H                                          55      CH.sub.3                                                                              CH.sub.3                                                                             3-CH.sub.3                                                                          5-CH.sub.3                                                                          H    oil                                   56      CH.sub.3                                                                              C.sub.2 H.sub.5                                                                      H     H     CH.sub.3                                   57      CH.sub.3                                                                              CH.sub.3                                                                             H     H     CH.sub.3                                   58      CH.sub.3                                                                              CH.sub.3                                                                             3-CH.sub.3                                                                          5-CH.sub.3                                                                          CH.sub.3                                   59      CH.sub.3                                                                              CH.sub.3                                                                             3-Cl  H     H    m.p. 48°                                                               (decomp.°)                     60      CH.sub.3                                                                              CH.sub.3                                                                             3-Br  H     CH.sub.3                                   61      CH.sub.3                                                                              CH.sub.3                                                                             3-CH.sub.3                                                                          H     H    decomposi-                                                                    tion from 70°                  62      CH.sub.3                                                                              CH.sub.3                                                                             3-Cl  H     CH.sub.3                                   63      CH.sub.3                                                                              CH.sub.3                                                                             3-Br  H     H                                          64      CH.sub.3                                                                              CH.sub.3                                                                             4-Cl  H     CH.sub.3                                   65      CH.sub.3                                                                              CH.sub.3                                                                             3-CH.sub.3                                                                          H     CH.sub.3                                   66      CH.sub.3                                                                              CH.sub.3                                                                             4-Cl  H     H                                          67      CH.sub.3                                                                              Br     4-Cl  H     H                                          68      CH.sub.3 O                                                                            CH.sub.3                                                                             H     H     H    oil                                   69      CH.sub.3 O                                                                            Cl     H     H     H                                          ______________________________________                                    

There are produced in an analogous manner the following compounds of theformula

    ______________________________________                                         ##STR18##                                                                    (R = CH.sub.3 ; R.sub.1 = 6-position)                                         Compound                                                                      No      R.sub.1 R.sub.2 R.sub.3                                                                             R.sub.4                                                                            Physical constants                         ______________________________________                                        70      CH.sub.3                                                                              H       H     H    m.p. 143-145°                       71      CH.sub.3                                                                              4-Cl    H     H                                               72      CH.sub.3                                                                              H       H     CH.sub.3                                                                           m.p. 176-180°                       73      C.sub.2 H.sub.5                                                                       H       H     H                                               74      Cl      H       H     H                                               75      Br      4-Cl    H     H                                               76      CH.sub.3                                                                              3-Br    H     H                                               77      CH.sub.3                                                                              3-CH.sub.3                                                                            H     CH.sub.3                                        78      CH.sub.3                                                                              3-CH.sub.3                                                                            H     H    m.p. 132-133°                       79      CH.sub.3                                                                              3-Cl    H     H    m.p. 65° (decomp.)                  80      CH.sub.3                                                                              3-CH.sub.3                                                                            5-CH.sub.3                                                                          H    m.p. 207-210°                       ______________________________________                                    

and also the following derivatives with R=--OCH₃ :

    ______________________________________                                        Comp.                               Physical                                  No.       R.sub.1 R.sub.2                                                                              R.sub.3                                                                             R.sub.4                                                                            constants                                 ______________________________________                                        81        CH.sub.3                                                                              H      H     H    m.p. 164-165°                      82        Cl      H      H     H    m.p. 152-153°                      83        Cl      4-Cl   H     H                                              84        Br      4-Br   H     H                                              85        Br      H      H     H                                              86        Cl      H      H     CH.sub.3                                       ______________________________________                                    

and the compounds ##STR19##

There are produced in an analogous manner the following compounds of theformula

    ______________________________________                                         ##STR20##                                                                    (R = CH.sub.3 ; R.sub.1 = 6-position)                                         Comp.                               Physical                                  No.    R.sub.1 R.sub.2  R.sub.3                                                                              R.sub.4                                                                            constants                                 ______________________________________                                        90     CH.sub.3                                                                              H        H      H    m.p. 142-146°                      91     CH.sub.3                                                                              H        H      CH.sub.3                                       92     C.sub.2 H.sub.5                                                                       H        H      H                                              93     Cl      H        H      H                                              94     CH.sub.3                                                                              4-Cl     H      H    m.p. 137-139°                      95     CH.sub.3                                                                              3-CH.sub.3                                                                             H      H    m.p. 112-113°                      96     CH.sub.3                                                                              4-Cl     H      CH.sub.3                                       97     CH.sub.3                                                                              3-CH.sub.3                                                                             5-CH.sub.3                                                                           H    oil                                       ______________________________________                                    

as well as the following derivatives with R=--OCH₃ :

    ______________________________________                                        Compound No.                                                                              R.sub.1  R.sub.2                                                                              R.sub.3                                                                              R.sub.4                                    ______________________________________                                         98         CH.sub.3 H      H      H    oil                                    99         Cl       H      H      H                                          100         Cl       4-Cl   H      H                                          101         Br       4-Br   H      H                                          102         Br       H      H      H                                          103         Cl       H      H      CH.sub.3                                   ______________________________________                                    

EXAMPLE 5

Production of ##STR21##

3-[N-(1,2-pyrazol-1-yl-acetyl)-N-(2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanone(compound No. 111)

(a) Production of 2-(1-pyrazolyl)-acetic acid

50 g of pyrazole in 250 ml of abs. tetrahydrofuran is added dropwise ina nitrogen atmosphere within 1/2 hour at 20°-30°, with stirring andcooling, to 38.7 g of sodium hydride in 100 ml of abs. tetrahydrofuran.The reaction mixture is stirred for a further 3 hours at 40°; it is thencooled towards 5° and, with good cooling, 160.7 g of bromoacetic acidethyl ester in 100 ml of abs. tetrahydrofuran is added dropwise at0°-10° during 1 hour. Stirring is maintained overnight at roomtemperature; there is then added dropwise 150 ml of ethanol; stirring iscontinued for 1 hour, and the suspension is subsequently concentrated byevaporation. To the residue is added a solution of 74 g of NaOH tabletsin 600 ml of 60% methanol (aqueous), and refluxing is carried out for 40minutes. The solution is then cooled, and washed twice with 200 ml ofether. The aqueous phase is made acid to a congo-red indicator (about pH2) with conc. hydrochloric acid at 5° with cooling, and the solution iscontinuously extracted during 24 hours with methylene chloride. Theextract is concentrated by evaporation, and recrystallised fromether/tetrahydrofuran. The crystals melts at 167°-169°.

(b) 165 g of 2-bromo-4-butyrolactone is slowly added at 10° C. to 135 gof 2,3,6-trimethylaniline and 106 g of sodium carbonate in 750 ml ofdimethylformamide, and the mixture is subsequently stirred for 16 hoursat 70° and for 24 hours at 100°. After cooling to +10°, there is added,with cooling, 1200 ml of ice water. Stirring is continued at 10° for 2hours; the precipitate is filtered off, and washed with water andpetroleum ether to yield3-[N-2,3,6-trimethylphenyl)]-amino-tetrahydro-2-furanone, m.p.108°-110°.

(c) 6.3 g of 2-(1-pyrazolyl)-acetic acid is placed into 200 ml oftoluene; 6.2 g of thionyl chloride is added, and the mixture is refluxedfor 1 hour. It is then cooled to 20°, and 11 g of the intermediateobtained according to (a) and 5.8 g of sodium carbonate are added. Afterstirring overnight at room temperature, ice water is added, andextraction is performed with methylene chloride; the extracts are washedwith water, dried over sodium sulphate and concentrated by evaporation.The resin remaining is purified through a silica gel column, and finallyfrozen out from ether at -50°. The vitreous diastereoisomeric mixture of3-[N-(1,2-pyrazol-1-yl-acetyl)-N-2,3,6-trimethylphenyl)]-amino-tetrahydrofuranonemelts at 50°-60°.

There are produced in an analogous manner the following compounds of theformula

    ______________________________________                                         ##STR22##                                                                    (R.sub.1 = 6-position)                                                        Compound  R        R.sub.1 R.sub.2                                                                              R.sub.3                                                                              R.sub.4                              ______________________________________                                        104       CH.sub.3 CH.sub.3                                                                              H      H      H                                    105       CH.sub.3 C.sub.2 H.sub.5                                                                       H      H      H                                    106       CH.sub.3 CH.sub.3                                                                              3-CH.sub.3                                                                           5-CH.sub.3                                                                           H                                    107       CH.sub.3 C.sub.2 H.sub.5                                                                       H      H      CH.sub.3                             108       CH.sub.3 CH.sub.3                                                                              H      H      CH.sub.3                             109       CH.sub.3 CH.sub.3                                                                              3-CH.sub.3                                                                           5-CH.sub.3                                                                           CH.sub.3                             110       CH.sub.3 CH.sub.3                                                                              3-Cl   H      H                                    111       CH.sub.3 CH.sub.3                                                                              3-CH.sub.3                                                                           H      H                                    112       CH.sub.3 CH.sub.3                                                                              3-CH.sub.3                                                                           H      CH.sub.3                             113       CH.sub.3 CH.sub.3                                                                              4-Cl   H      H                                    114       CH.sub.3 O                                                                             CH.sub.3                                                                              H      H      H                                    ______________________________________                                    

The compounds of the formula I can be used on their own or together withsuitable carriers and/or other additives. Suitable carriers andadditives can be solid or liquid and they correspond to the substancescommon in formulation practice, such as natural or regenerated mineralsubstances, solvents, dispersing agents, wetting agents, adhesives,thickeners, binders and/or fertilisers.

The content of active substance in commercial compositions is between0.1 and 90%.

For application, the compounds of the formula I can be in the followingforms (the weight-percentage figures in brackets signify advantageousamounts of active substance):

solid preparations: dusts and scattering agents (up to 10%), granulates[coated granules, impregnated granules and homogeneous granules] (1 to80%);

liquid preparations:

(a) water-dispersible concentrates of active substance: wettable powdersand pastes (25 to 90% in the commercial packing, 0.01 to 15% inready-for-use solutions); emulsion concentrates and solutionconcentrates 10 to 50%, 0.01 to 15% in ready-for-use solutions);

(b) solutions (0.1 to 20%).

The active substances of the formula I of the present invention can beformulated for example as follows.

Dust: The following substances are used to produce (a) a 5% dust and (b)a 2% dust:

(a) 5 parts of active substance,

95 parts of talcum;

(b) 2 parts of active substance, 1 part of highly dispersed silicicacid, and 97 parts of talcum.

The active substances are mixed and ground with the carriers, and inthis form they can be applied by dusting.

Granulate: The following substances are used to produce a 5% granulate:

5 parts of active substance,

0.25 part of epichlorohydrin,

0.25 part of cetyl polyglycol ether,

3.50 parts of polyethylene glycol, and

91 parts of kaolin (particle size 0.3-0.8 mm).

The active substance is mixed with epichlorohydrin and dissolved in 6parts of acetone; the polyethylene glycol and cetyl polyglycol ether arethen added. The solution thus obtained is sprayed onto kaolin, and theacetone is subsequently evaporated off in vacuo. A microgranulate ofthis kind is particularly suitable for soil application.

Wettable powder: The following constituents are used to produce (a) a70% wettable powder, (b) a 40% wettable powder, (c) and (d) a 25%wettable powder, and (e) a 10% wettable powder:

(a) 70 parts of active substance, 5 parts of sodiumdibutylnaphthylsulphonate, 3 parts of naphthalenesulphonicacid/phenolsulphonic acid/formaldehyde condensate 3:2:1, 10 parts ofkaolin, and 12 parts of Champagne chalk;

(b) 40 parts of active substance, 5 parts of sodium lignin sulphonate, 1part of sodium dibutylnaphthalenesulphonate, and 54 parts of silicicacid;

(c) 25 parts of active substance, 4.5 parts of calcium ligninsulphonate, 1.9 parts of Champagne chalk/hydroxyethylcellulose mixture(1:1), 1.5 parts of sodium dibutylnaphthalenesulphonate, 19.5 parts ofsilicic acid, 19.5 parts of Champagne chalk, and 28.1 parts of kaolin;

(d) 25 parts of active substance, 2.5 parts ofisooctylphenoxy-polyoxyethylene-ethanol, 1.7 parts of Champagnechalk/hydroxyethylcellulose mixture (1:1), 8.3 parts of sodium aluminiumsilicate, 16.5 parts of kieselguhr, and 46 parts of kaolin; and

(e) 10 parts of active substance, 3 parts of a mixture of the sodiumsalts of saturated fatty alcohol sulphates, 5 parts ofnaphthalenesulphonic acid/formaldehyde condensate, and 82 parts ofkaolin.

The active substances are intimately mixed in suitable mixers with theadditives, and the mixture is then ground in the appropriate mills androllers. There are obtained wettable powders which have excellentwetting and suspension properties, which can be diluted with water togive suspensions of the desired concentration, and which can be used inparticular for leaf application.

Emulsifiable concentrate: The following substances are used to produce a25% emulsifiable concentrate:

25 parts of active substance,

2.5 parts of epoxidised vegetable oil,

10 parts of an alkylarylsulphonate/fatty alcohol polyglycol ethermixture,

5 parts of dimethylformamide, and

57.5 parts of xylene.

Emulsions of the desired concentration can be prepared from theseconcentrates by dilution with water; and these emulsions areparticularly suitable for leaf application.

In order to adapt them to suit prevailing circumstances, the compoundsof the formula I can be used, for widening their sphere of action,together with other suitable pesticides, such as fungicides,insecticides, acaricides, nematocides, rodenticides or herbicides, orwith active substances affecting plant growth and also with fertilisers.

EXAMPLE 6 Action against Phytophthora infestans on tomatoes

(I) Curative action

Tomato plants of the variety "Roter Gnom" are sprayed, after threeweeks' cultivation, with a zoospore suspension of the fungus, andincubated in a chamber at 18° to 20° with saturated atmospherichumidity. The incubation treatment is interrupted after 24 hours; theplants are dried and then sprayed with a liquor containing the activesubstance in the form of a wettable powder at a concentration of 0.06%and 0.02%. The applied coating is allowed to dry, and the plants aresubsequently returned to the moist-atmosphere chamber for 4 days. Thenumber and size of the typical leaf spots appearing after this timeserve as a criterion for an assessment of the effectiveness of thesubstances tested. Compounds of the formula I consistently produced, atan active-substance concentration of 0.06%, a reduction of fungusinfestation to less than 20%. The compounds Nos. 1, 2, 5, 12, 19, 24,28, 30, 33, 51, 61, 70, 79, 80, 82, 89, 90, 95, 98, 111 and othersbrought about at this concentration a reduction of fungus infestation to0-5%. At the concentration of active substance of 0.02%, a reduction offungus infestation to 0-5% was produced by, inter alia, the compoundsNos. 1, 2, 5, 12, 19, 28, 30, 33, 70, 79, 80, 90 and 95. Nophytotoxicity was observed.

(II) Preventitive systemic action

The active substance in the form of a wettable powder is applied in aconcentration of 0.006% (relative to the volume of soil) to the surfaceof the soil around 3-week old potted tomato plants of the "Roter Gnom"variety. After a period of three days, the under side of the leaves ofthe plants is sprayed with a zoospore suspension of Phytophthorainfestans. The plants are then stored for 5 days in a spray chamber at18°-20° with a saturated atmosphere. The typical leaf spots appear afterthis time; on the basis of their number and size, an evaluation is thenmade of the effectiveness of the substances tested.

The tomato plants treated with compounds of the formula I showedconsistently less than 20% fungus infestation, compared with thatexhibited by control plants (=100% infestation). The compounds Nos. 1,2, 5, 12, 19, 24, 28, 30, 33, 51, 61, 70, 78, 79, 80, 82, 88, 89, 90,95, 98, 104, 106, 111 and others prevented fungus infestation completelyor almost completely (0-5% infestation).

EXAMPLE 7 Action against Pythium debaryanum on sugar beet

(a) Action after soil application

The fungus is cultivated on sterile oat seeds and thus added to asoil/sand mixture. The soil infested in this way is filled into flowerpots and sown with sugar-beet seeds. Immediately after sowing, the testpreparations formulated as wettable powder are poured as aqueoussuspensions over the soil (20 ppm of active substance relative to thevolume of soil). The pots are then placed in a greenhouse at 20-24° for2-3 weeks. The soil during this time is kept uniformly moist by a lightspraying with water. In the assessment of the tests, the sprouting ofthe sugar-beet plants and also the proportion of healthy plants and ofdiseased plants is determined. After the treatment with the activesubstances of the formula I, more than 80% of the sugar-beet plants weresprouting and had a healthy appearance. This result was obtained alsowith an active-substance concentration in the soil of 6 ppm with use ofthe compounds Nos. 1, 2, 4, 5, 9, 12, 13, 15, 16, 19, 30, 33, 37, 59,61, 79, 95, 104, 111 and others.

(b) Action after application as dressing

The fungus is cultivated on sterile oat seeds and thus added to asoil/sand mixture. The soil infested in this manner is filled intoflower pots, and sown with sugar-beet seeds which have been dressed withthe test preparations formulated as dressing powder (1000 ppm of activesubstance relative to the weight of seed.) The sown pots are placed in agreenhouse at 20°-24° for 2-3 weeks. The soil during this time is keptuniformly moist by a light spraying with water. In the assessment of thetests, the sprouting of the sugar-beet plants and also the proportion ofhealthy plants and of diseased plants is determined.

After the treatment with active substances of the formula I, more than80% of the sugar-beet plants were sprouting and had a healthyappearance.

We claim:
 1. A compound of the formula I ##STR23## wherein R representsC₁ -C₄ -alkyl, C₁ -C₄ -alkoxy or halogen,R₁ represents C₁ -C₃ -alkyl, C₁-C₄ -alkoxy or halogen, R₂ represents hydrogen, C₁ -C₃ -alkyl, C₁ -C₄-alkoxy or halogen, R₃ represents hydrogen or methyl, with the totalnumber of C atoms of the substituents R, R₁, R₂ and R₃ in the phenylring not exceeding the number 8, R₄ represents hydrogen or methyl, andR₅ represents an alkylthioalkyl or alkoxyalkyl group having 2 to 5carbon atoms.
 2. A compound according to claim 1 wherein R representsmethyl, R₁ represents methyl, ethyl, chlorine or bromine, R₂ representshydrogen, halogen or methyl, R₃ represents hydrogen or methyl, R₄represents hydrogen or methyl.
 3. A compound according to claim 2,wherein R₅ represents methoxymethyl or ethoxymethyl. 4.3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-aminotetrahydro-2-furanoneaccording to claim
 3. 5.3-[N-(ethoxyacetyl)-N-(2,6-dimethylphenyl)]-aminotetrahydro-2-furanoneaccording to claim
 3. 6.3-[N-(methoxyacetyl)-N-(2,6-dimethyl-2-chlorophenyl)]-amino-tetrahydro-2-furanoneaccording to claim
 3. 7.3-[N-(ethoxyacetyl)-N-(2,6-dimethyl-3-chlorophenyl)]-amino-tetrahydro-2-furanoneaccording to claim
 3. 8.3-[N-(methoxyacetyl)-N-(2,6-dimethylphenyl)]-amino-5-methyltetrahydro-2-furanoneaccording to claim
 3. 9.3-[N-(methoxyacetyl)-N-(2,3,5,6-tetramethylphenyl)]-amino-tetrahydro-2-furanoneaccording to claim
 3. 10. A process for combating phytopathogenic fungiwhich comprises applying to the locus thereof a fungicidally effectiveamount of a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7,8 or
 9. 11. A fungicidal composition containing as active substance afungicidally effective amount of a compound according to any one ofclaims 1, 2, 3, 4, 5, 6, 7, 8 or 9 together with a suitable inertcarrier therefor. 12.3-[N-(methoxyacetyl)-N-(2,3,6-trimethylphenyl)amino]-tetrahydro-2-furanoneaccording to claim 4.